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Sexually Transmitted Infections Feb 2011Ocular syphilis among HIV-infected patients continues to be a problem in the highly active antiretroviral therapy (HAART) era. However, outside of case reports or small... (Review)
Review
BACKGROUND
Ocular syphilis among HIV-infected patients continues to be a problem in the highly active antiretroviral therapy (HAART) era. However, outside of case reports or small case series, little is known about the clinical, laboratory, and treatment outcomes of these patients. Objective To examine the literature on HIV-infected patients and determine the results of treatment.
METHODS
Systematic review of cases series and case reports among HIV-infected individuals with ocular syphilis. Reviews, languages other than English and pre-1980 reports were excluded. The effect of CD4 count and virological suppression on clinical manifestations and diagnostic laboratory values was evaluated.
RESULTS
A total of 101 HIV-infected individuals in case series and case reports were identified. Ocular syphilis led to the HIV diagnosis in 52% of cases, including patients with CD4 count >200 cells/mm(3). Posterior uveitis was significantly more common in individuals with CD4 count <200 cells/mm(3) (p = 0.002). Three patients with confirmed ocular syphilis had negative non-treponemal tests. Ninety-seven per cent of patients with visual impairment improved following intravenous penicillin or ceftriaxone.
CONCLUSIONS
Non-treponemal tests may be negative in HIV-infected patients with ocular syphilis. Ocular syphilis remains an important clinical manifestation that can lead to initial HIV diagnosis.
Topics: Adult; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Eye Infections, Bacterial; Female; HIV Infections; HIV-1; Humans; Male; Middle Aged; RNA, Viral; Syphilis; Young Adult
PubMed: 20798396
DOI: 10.1136/sti.2010.043042 -
The Cochrane Database of Systematic... May 2017Micronutrient deficiencies are common among adults living with HIV disease, particularly in low-income settings where the diet may be low in essential vitamins and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Micronutrient deficiencies are common among adults living with HIV disease, particularly in low-income settings where the diet may be low in essential vitamins and minerals. Some micronutrients play critical roles in maintenance of the immune system, and routine supplementation could therefore be beneficial. This is an update of a Cochrane Review previously published in 2010.
OBJECTIVES
To assess whether micronutrient supplements are effective and safe in reducing mortality and HIV-related morbidity of HIV-positive adults (excluding pregnant women).
SEARCH METHODS
We performed literature searches from January 2010 to 18 November 2016 for new randomized controlled trials (RCTs) of micronutrient supplements since the previous review included all trials identified from searches prior to 2010. We searched the CENTRAL (the Cochrane Library), Embase, and PubMed databases. Also we checked the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and the ClinicalTrials.gov trials registers. We also checked the reference lists of all new included trials.
SELECTION CRITERIA
We included RCTs that compared supplements that contained either single, dual, or multiple micronutrients with placebo, no treatment, or other supplements. We excluded studies that were primarily designed to investigate the role of micronutrients for the treatment of HIV-positive participants with metabolic morbidity related to highly active antiretroviral therapy (HAART). Primary outcomes included all-cause mortality, morbidity, and disease progression.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion, and appraised trial quality for risk of bias. Where possible, we presented results as risk ratios (RR) for dichotomous variables, as hazard ratios (HRs) for time-to-event data, and as mean differences (MD) for continuous variables, each with 95% confidence intervals (CIs). Since we were often unable to pool the outcome data, we tabulated it for each comparison. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included 33 trials with 10,325 participants, of which 17 trials were new trials. Ten trials compared a daily multiple micronutrient supplement to placebo in doses up to 20 times the dietary reference intake, and one trial compared a daily standard dose with a high daily dose of multivitamins. Nineteen trials compared supplementation with single or dual micronutrients (such as vitamins A and D, zinc, and selenium) to placebo, and three trials compared different dosages or combinations of micronutrients. Multiple micronutrientsWe conducted analyses across antiretroviral therapy (ART)-naive adults (3 trials, 1448 participants), adults on antiretroviral therapy (ART) (1 trial, 400 participants), and ART-naive adults with concurrent active tuberculosis (3 trials, 1429 participants). Routine multiple micronutrient supplementation may have little or no effect on mortality in adults living with HIV (RR 0.91, 95% CI 0.72 to 1.15; 7 trials, 2897 participants, low certainty evidence).Routine supplementation for up to two years may have little or no effect on the average of mean CD4+ cell count (MD 26.40 cells/mm³, 95% CI -22.91 to 75.70; 6 trials, 1581 participants, low certainty evidence), or the average of mean viral load (MD -0.1 logviral copies, 95% CI -0.26 to 0.06; 4 trials, 840 participants, moderate certainty evidence). One additional trial in ART-naïve adults did report an increase in the time to reach a CD4+ cell count < 250 cells/mm³ after two years of high dose supplementation in Botswana (HR 0.48, 95% CI 0.26 to 0.88; 1 trial, 439 participants). However, the trial authors reported this effect only in the trial arm that received multiple micronutrients plus selenium (not either supplementation alone), which is inconsistent with the findings of other trials that used similar combinations of micronutrients and selenium.In one additional trial that compared high-dose multiple micronutrient supplementation with standard doses in people on ART, peripheral neuropathy was lower with high dose supplements compared to standard dose (incidence rate ratio (IRR) 0.81, 95% CI 0.7 to 0.94; 1 trial, 3418 participants), but the trial was stopped early due to increased adverse events (elevated alanine transaminase (ALT) levels) in the high dose group. Single or dual micronutrientsNone of the trials of single or dual micronutrient supplements were adequately powered to assess for effects on mortality or morbidity outcomes. No clinically significant changes in CD4 cell count (data not pooled, 14 trials, 2370 participants, very low or low certainty evidence) or viral load (data not pooled, seven studies, 1334 participants, very low or low certainty evidence), were reported. Supplementation probably does increase blood concentrations of vitamin D and zinc (data not pooled, vitamin D: 4 trials, 299 participants, zinc: 4 trials, 484 participants, moderate certainty evidence) and may also increase blood concentrations of vitamin A (data not pooled, 3 trials, 495 participants, low certainty evidence), especially in those who are deficient.
AUTHORS' CONCLUSIONS
The analyses of the available trials have not revealed consistent clinically important benefits with routine multiple micronutrient supplementation in people living with HIV. Larger trials might reveal small but important effects.These findings should not be interpreted as a reason to deny micronutrient supplements for people living with HIV where specific deficiencies are found or where the person's diet is insufficient to meet the recommended daily allowance of vitamins and minerals.
Topics: Adult; CD4 Lymphocyte Count; Cause of Death; Child; Dietary Supplements; Female; HIV Infections; HIV-1; HIV-2; Hospitalization; Humans; Micronutrients; Pregnancy; Pregnancy Complications, Infectious; Randomized Controlled Trials as Topic; Selenium; Viral Load; Vitamin A; Vitamin D; Vitamins; Zinc; beta Carotene
PubMed: 28518221
DOI: 10.1002/14651858.CD003650.pub4 -
Human Reproduction Update 2009Adaptation of the maternal immune response to accommodate the semi-allogeneic fetus is necessary for pregnancy success, and disturbances in maternal tolerance are... (Review)
Review
BACKGROUND
Adaptation of the maternal immune response to accommodate the semi-allogeneic fetus is necessary for pregnancy success, and disturbances in maternal tolerance are implicated in infertility and reproductive pathologies. T regulatory (Treg) cells are a recently discovered subset of T-lymphocytes with potent suppressive activity and pivotal roles in curtailing destructive immune responses and preventing autoimmune disease.
METHODS
A systematic review was undertaken of the published literature on Treg cells in the ovary, testes, uterus and gestational tissues in pregnancy, and their link with infertility, miscarriage and pathologies of pregnancy. An overview of current knowledge on the generation, activation and modes of action of Treg cells in controlling immune responses is provided, and strategies for manipulating regulatory T-cells for potential applications in reproductive medicine are discussed.
RESULTS
Studies in mouse models show that Treg cells are essential for maternal tolerance of the conceptus, and that expansion of the Treg cell pool through antigen-specific and antigen non-specific pathways allows their suppressive actions to be exerted in the critical peri-implantation phase of pregnancy. In women, Treg cells accumulate in the decidua and are elevated in maternal blood from early in the first trimester. Inadequate numbers of Treg cells or their functional deficiency are linked with infertility, miscarriage and pre-eclampsia.
CONCLUSIONS
The potency and wide-ranging involvement of Treg cells in immune homeostasis and disease pathology indicates the considerable potential of these cells as therapeutic agents, raising the prospect of their utility in novel treatments for reproductive pathologies.
Topics: Abortion, Spontaneous; Animals; Cytokines; Dendritic Cells; Female; Humans; Immune Tolerance; Indoleamine-Pyrrole 2,3,-Dioxygenase; Infertility; Male; Mice; Models, Immunological; Ovary; Pregnancy; Pregnancy Complications; Prostaglandins; Semen; Signal Transduction; T-Lymphocytes, Regulatory; Testis; Toll-Like Receptors
PubMed: 19279047
DOI: 10.1093/humupd/dmp004 -
Multiple Sclerosis and Related Disorders Jan 2023Treatment with cladribine tablets (CladT), an immune reconstitution therapy for relapsing multiple sclerosis (RMS), involves two short courses of treatment in Year 1 and... (Review)
Review
BACKGROUND
Treatment with cladribine tablets (CladT), an immune reconstitution therapy for relapsing multiple sclerosis (RMS), involves two short courses of treatment in Year 1 and Year 2. Most patients achieve sustained efficacy with CladT, but a small proportion may experience new disease activity (DA). Following completion of the indicated dose, physicians may have questions relating to the long-term management of these patients. Since the EU approval of CladT over 5 years ago, real-world evidence (RWE) is increasing and may provide some insights and guidance for clinical practice. We describe a systematic literature review (SLR) of RWE and provide expert opinions relating to six questions regarding the long-term use of CladT.
METHODS
Pertinent clinical questions were developed by a steering committee (SC) of 14 international multiple sclerosis (MS) experts regarding breakthrough DA in Year 1, new DA after 2 years or more of treatment, long-term management of stable patients, and whether additional courses of CladT may be required or safe. An SLR was performed in EMBASE and PubMed using the population, intervention, comparators, outcomes, study design (PICOS) framework to identify relevant studies within the last 15 years. Searches of key congress proceedings for the last 2-3 years were also performed. Following review of the results and RWE, the SC drafted and agreed on expert opinion statements for each question.
RESULTS
A total of 35 publications reporting RWE for CladT were included in this review. In the real world, breakthrough DA in Year 1 is of low incidence (1.1-21.9%) but can occur, particularly in patients switching from anti-lymphocyte trafficking agents. In most patients, this DA did not lead to treatment discontinuation. Reported rates of DA after the full therapeutic effect of CladT has been achieved (end of Year 2, 3 or 4) range from 12.0 to 18.7% in the few studies identified. No RWE was identified to support management decisions for stable patients in Year 5 or later. Views among the group were also diverse on this question and voting on expert opinion statements was required. Only two studies reported the administration of additional courses of CladT, but detailed safety outcomes were not provided.
CONCLUSIONS
RWE for the long-term use of CladT in the treatment of RMS is increasing, however, gaps in knowledge remain. Where possible, the RWE identified through the SLR informed expert statements, but, where RWE is still lacking, these were based solely on experiences and opinion, providing some guidance on topics and questions that occur in daily clinical practice. More real-world studies with longer-term follow-up periods are needed and highly anticipated.
Topics: Humans; Cladribine; Multiple Sclerosis; Expert Testimony; Lymphocytes; Tablets; Recurrence; Immunosuppressive Agents
PubMed: 36565573
DOI: 10.1016/j.msard.2022.104459 -
International Journal of Molecular... Oct 2022Environmental Enrichment (EE) is based on the promotion of socio-environmental stimuli, which mimic favorable environmental conditions for the practice of physical... (Review)
Review
Environmental Enrichment (EE) is based on the promotion of socio-environmental stimuli, which mimic favorable environmental conditions for the practice of physical activity and health. The objective of the present systematic review was to evaluate the influence of EE on pro-and anti-inflammatory immune parameters, but also in cell activation related to the innate and acquired immune responses in the brain and peripheral tissues in rodents. Three databases [PubMed (2209 articles), Scopus (1154 articles), and Science Direct (1040 articles)] were researched. After applying the eligibility criteria, articles were selected for peer review, independently, as they were identified by September 2021. The protocol for this systematic review was registered in the PROSPERO. Of the 4417 articles found, 16 were selected for this systematic review. In the brain, EE promoted a reduction in proinflammatory cytokines and chemokines. In the blood, EE promoted a higher percentage of leukocytes, an increase in CD19+ B lymphocytes, and the proliferation of Natura Killer (NK cells). In the bone marrow, there was an increase in the number of CD27- and CD11b+ mature NK cells and a reduction in CD27- and CD11b+ immature Natural Killer cells. In conclusion, EE can be an immune modulation approach and plays a key role in the prevention of numerous chronic diseases, including cancer, that have a pro-inflammatory response and immunosuppressive condition as part of their pathophysiology.
Topics: Animals; Bone Marrow; Cytokines; Killer Cells, Natural; Rodentia
PubMed: 36233282
DOI: 10.3390/ijms231911986 -
Haematologica May 2011Chronic lymphocytic leukemia is frequently associated with immune disturbances. The relationship between chronic lymphocytic leukemia and autoimmune cytopenias,... (Review)
Review
Chronic lymphocytic leukemia is frequently associated with immune disturbances. The relationship between chronic lymphocytic leukemia and autoimmune cytopenias, particularly autoimmune hemolytic anemia and immune thrombocytopenia, is well established. The responsible mechanisms, particularly the role of leukemic cells in orchestrating the production of polyclonal autoantibodies, are increasingly well understood. Recent studies show that autoimmune cytopenia is not necessarily associated with poor prognosis. On the contrary, patients with anemia or thrombocytopenia due to immune mechanisms have a better outcome than those in whom these features are due to bone marrow infiltration by the disease. Moreover, fears about the risk of autoimmune hemolysis following single agent fludarabine may no longer be appropriate in the age of chemo-immunotherapy regimens. However, treatment of patients with active hemolysis may pose important problems needing an individualized and clinically sound approach. The concept that autoimmune cytopenia may precede the leukemia should be revisited in the light of recent data showing that autoimmune cytopenia may be observed in monoclonal B-cell lymphocytosis, a condition that can only be detected by using sensitive flow cytometry techniques. On the other hand, there is no evidence of an increased risk of non-hemic autoimmune disorders in chronic lymphocytic leukemia. Likewise, there is no epidemiological proof of an increased risk of chronic lymphocytic leukemia in patients with non-hemic autoimmunity. Finally, since immune disorders are an important part of chronic lymphocytic leukemia, studies aimed at revealing the mechanisms linking the neoplastic and the immune components of the disease should help our understanding of this form of leukemia.
Topics: Anemia, Hemolytic, Autoimmune; Autoantibodies; Autoimmunity; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Models, Immunological; Thrombocytopenia
PubMed: 21242190
DOI: 10.3324/haematol.2010.036152 -
Medicine Aug 2018Several studies have shown that B7-H4 expression is significantly increased in ovarian cancer. However, the role of B7-H4 expression in ovarian cancer remains unclear,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several studies have shown that B7-H4 expression is significantly increased in ovarian cancer. However, the role of B7-H4 expression in ovarian cancer remains unclear, and some studies reporting conflicting results. A systematic review of the literature and meta-analysis were conducted to assess the clinicopathologic characteristics and prognostic significance of B7-H4 in ovarian cancer.
METHODS
Eligible studies were searched in the PubMed, MEDLINE, Cochrane Library, and the China National Knowledge Infrastructure databases. The included studies assessed the relationship between B7-H4 expression and clinicopathologic features or prognosis in patients with ovarian cancer through September 2017. A total of 1045 patients in 10 studies were included in the meta-analysis. Stata software version 12.0 was used to analyze the data. We used an odds ratio (OR) or hazard ratio (HR) with a 95% confidence interval (CI) to assess the risk or hazard association.
RESULTS
B7-H4 expression in ovarian cancer patients was significantly increased (OR: 4.20, 95% CI: 2.85-6.18, Z = 6.91, P < .05), and heterogeneity was low between studies (I = 8.2%, P = .366). With respect to the clinicopathologic features, no relation was detected between B7-H4 expression and International Federation of Gynaecology and Obstetricsstages stages (OR: 0.81, 95% CI: 0.64-1.03, Z = 1.70, P = .09), pathologic grade (OR: 0.91, 95% CI: 0.72-1.16, Z = 0.76, P = .45), tumor metastasis (OR: 1.25, 95% CI: 0.90-1.74, Z = 1.34, P = .18), or histologic type (OR: 1.17, 95% CI: 0.85-1.60, Z = 0.96, P = .34) in ovarian cancer. Furthermore, B7-H4 expression was significantly associated with a worse progression-free survival (PFS) (HR: 1.30, 95% CI: 1.17-1.45, Z = 4.79, P < .05).
CONCLUSION
B7-H4 expression was related to ovarian cancer, but not to patients' clinicopathologic characteristics. High B7-H4 expression was negatively correlated with survival outcome, suggesting that B7-H4 plays an essential role in poor prognosis in ovarian cancer patients.
Topics: Biomarkers, Tumor; China; Disease-Free Survival; Female; Humans; Neoplasm Staging; Ovarian Neoplasms; Prognosis; T-Lymphocytes; V-Set Domain-Containing T-Cell Activation Inhibitor 1
PubMed: 30095655
DOI: 10.1097/MD.0000000000011821 -
Oncoimmunology 2020: Despite the improvement in therapeutic interventions, 5-year survival rates in Head and Neck Squamous Cell Carcinoma (HNSCC) are limited. HNSCC is an immunogenic... (Meta-Analysis)
Meta-Analysis
: Despite the improvement in therapeutic interventions, 5-year survival rates in Head and Neck Squamous Cell Carcinoma (HNSCC) are limited. HNSCC is an immunogenic cancer type for which molecular stratification markers are lacking. Tumor-infiltrating lymphocytes (TILs) have shown a favorable prognostic role in different cancer types. This study focused on the prognostic role of NK cells in HNSCC. : A systematic search was conducted in Pubmed/Medline and Embase. Articles that correlated the presence of intratumoral NK cells, activating/inhibiting receptors, death receptors, or their ligands with clinicopathologic characteristics or survival were included. A meta-analysis was performed that assessed the association between CD56+ and CD57+ and overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). : A pooled analysis indicated a favorable prognostic role of CD56+ and CD57+ NK cells for OS (HR 0.19 CI 0.11-0.35). NK cell markers NKp46 and Granzyme B (GrB) also have a favorable prognostic role. NK cell ligand Fas correlated with better survival and better characteristics. NK cell marker Fas-L, NK cell ligands CEACAM1, RCAS1, CD70 and TRAIL-R, and effector molecules of these ligands, FADD and FAP1, correlated to features of worse prognosis. : A favorable prognostic role of NK cells in HNSCC was found in this review. Some studies implied the opposite, indicating the fine balance between pro- and anti-tumor functions of NK cells. Future studies using homogeneous patient cohorts regarding tumor subsite and treatment modality, are necessary to further provide insight into the prognostic role of NK cells.
Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Killer Cells, Natural; Ligands; Prognosis; Squamous Cell Carcinoma of Head and Neck
PubMed: 32363116
DOI: 10.1080/2162402X.2020.1747345 -
Frontiers in Immunology 2021HIV infection results in immune homeostasis perturbations, which is characterized by CD4 T-cell depletion, immune activation, and inflammation. Effective antiretroviral... (Meta-Analysis)
Meta-Analysis
HIV infection results in immune homeostasis perturbations, which is characterized by CD4 T-cell depletion, immune activation, and inflammation. Effective antiretroviral therapy (ART) does not fully restore immunologic and clinical health in people living with HIV (PLWH). Various drugs have been used to improve their immune status and CD4 T-cell counts, but no measures have been tested effective. Here we conduct a systematic review and meta-analysis of existing clinical studies on improving CD4 T-cell count while decreasing inflammation and immune activation. We retrieved possible relevant publications from a total of five electronic databases and selected eligible studies, which dealt with outcomes of medical therapy for CD4 T-cell count recovery, inflammation, and immune activation with or without ART. We paid particular attention to immunologic non-responders with a favorable treatment regimen. Thirty-three articles were included in the systematic review and meta-analysis. However, there were no safe and effective medications specific for improving CD4 T-cell reconstitution. The immunological benefits or adverse events mainly depend on the safety, dosage, and duration of the candidate medication use, as well as whether it is combined with ART. Under the "safe, combined, adequate and long (SCAL)" principles, alternative approaches are needed to accelerate the recovery of CD4 T-cells, and to prevent adverse long-term outcomes in PLWH with standard ART treatment.
Topics: CD4-Positive T-Lymphocytes; HIV Infections; HIV Long-Term Survivors; HIV-1; Humans; Immunity; Immunomodulation; Inflammation
PubMed: 33679779
DOI: 10.3389/fimmu.2021.632119 -
PloS One 2014A network meta-analysis can provide estimates of relative efficacy for treatments not directly studied in head-to-head randomized controlled trials. We estimated the... (Meta-Analysis)
Meta-Analysis Review
48-week efficacy and safety of dolutegravir relative to commonly used third agents in treatment-naive HIV-1-infected patients: a systematic review and network meta-analysis.
BACKGROUND
A network meta-analysis can provide estimates of relative efficacy for treatments not directly studied in head-to-head randomized controlled trials. We estimated the relative efficacy and safety of dolutegravir (DTG) versus third agents currently recommended by guidelines, including ritonavir-boosted atazanavir (ATV/r), ritonavir-boosted darunavir (DRV/r), efavirenz (EFV), cobicistat-boosted elvitegravir (EVG/c), ritonavir-boosted lopinavir (LPV/r), raltegravir (RAL), and rilpivirine (RPV), in treatment-naive HIV-1-infected patients.
METHODS
A systematic review of published literature was conducted to identify phase 3/4 randomized controlled clinical trials (up to August 2013) including at least one third agent of interest in combination with a backbone nucleoside reverse transcriptase inhibitor (NRTI) regimen. Bayesian fixed-effect network meta-analysis models adjusting for the type of nucleoside reverse transcriptase inhibitor backbone (tenofovir disoproxil fumarate/emtricitabine [TDF/FTC] or abacavir/lamivudine [ABC/3TC]) were used to evaluate week 48 efficacy (HIV-RNA suppression to <50 copies/mL and change in CD4+ cells/µL) and safety (lipid changes, adverse events, and discontinuations due to adverse events) of DTG relative to all other treatments. Sensitivity analyses assessing the impact of NRTI treatment adjustment and random-effects models were performed.
RESULTS
Thirty-one studies including 17,000 patients were combined in the analysis. Adjusting for the effect of NRTI backbone, treatment with DTG resulted in significantly higher odds of virologic suppression (HIV RNA<50 copies/mL) and increase in CD4+ cells/µL versus ATV/r, DRV/r, EFV, LPV/r, and RPV. Dolutegravir had better or equivalent changes in total cholesterol, LDL, triglycerides, and lower odds of adverse events and discontinuation due to adverse events compared to all treatments. Random-effects and unadjusted models resulted in similar conclusions.
CONCLUSION
Three clinical trials of DTG have demonstrated comparable or superior efficacy and safety to DRV, RAL, and EFV in HIV-1-infected treatment-naive patients. This network meta-analysis suggests DTG is also favorable or comparable to other commonly used third agents (ATV/r, LPV/r, RPV, and EVG/c).
Topics: Adenine; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Deoxycytidine; Dideoxynucleosides; Drug Combinations; Emtricitabine; HIV Infections; HIV-1; Heterocyclic Compounds, 3-Ring; Humans; Lamivudine; Lipids; Lopinavir; Nitriles; Organophosphonates; Oxazines; Piperazines; Pyridones; Pyrimidines; Pyrrolidinones; Raltegravir Potassium; Randomized Controlled Trials as Topic; Rilpivirine; Ritonavir; Tenofovir; Time Factors; Treatment Outcome; Viral Load
PubMed: 25188312
DOI: 10.1371/journal.pone.0105653